Rates and determinants of decreased bone health among HIV-infected patients

HIV 感染者骨骼健康状况下降的比率和决定因素

• 批准号: 8590186
• 负责人: Roger Bedimo
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590186
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Aging; Analysis of Variance; Anti-Retroviral Agents; Body mass index; Bone Density; Caring; Chronic; Clinical; Code; Confounding Factors (Epidemiology); Control Groups; Cox Proportional Hazards Models; Cross-Sectional Studies; Data; Databases; Drug usage; Dyslipidemias; Endocrine system; Evaluation; Evaluation of Risk Factors; Fracture; Gender; General Population; Gonadal Hormones; Guidelines; HIV; HIV Infections; HIV Seropositivity; Health; Healthcare Systems; Hepatitis C; Hepatitis C virus; High Prevalence; Highly Active Antiretroviral Therapy; Hyperglycemia; ICD-9; Incidence; Infection; Inflammatory; Insulin Resistance; Knowledge; Lead; Malnutrition; Mediating; Metabolic; Modeling; Mono-S; Morbidity - disease rate; Osteoporosis; Outcome; Pathogenesis; Patients; Population; Race; Registries; Risk; Risk Factors; Role; Smoking; Source; Steroids; Subgroup; Survival Analysis; Testing; Texas; Time; Veterans; Vitamin D; Work; aging population; antiretroviral therapy; bone health; bone loss; bone mass; bone turnover; clinical risk; cohort; cytokine; data registry; health administration; high risk; improved; mortality; osteoporosis with pathological fracture; screening; trend

DESCRIPTION (provided by applicant): With the improved survival of HIV-infected patients since the introduction of Highly Active Antiretroviral Therapy (HAART), low bone mass and osteoporotic fractures seem to be emerging as important chronic problems that affect the aging HIV-positive population. Furthermore, an estimated 15 to 30% of HIV-infected patients are co-infected with hepatitis C (HCV), also associated with osteoporosis. For a given decrease in bone mineral density (BMD), the fracture risk increases dramatically with age in the general population. Despite this fact, trends in fracture risk in a large HIV cohort have never been evaluated to determine whether this is a growing problem among HIV-infected patients nor has an in-depth evaluation of risk factors been conducted, including type and duration of antiretroviral therapy (ART) and HCV co-infection. Furthermore, factors associated with HCV infection that might mediate a higher risk of decreased bone density and osteoporotic fractures - either decreased formation or increased resorption - among HIV-infected patients have not been elucidated. Finally, the impact of osteoporotic fractures on AIDS-related and non-AIDS-related morbidity and mortality is not known. We propose to help bridge these gaps in knowledge with a combination of: 1) a retrospective analysis of osteoporotic fracture risk, their predictors and outcomes in the Veterans Health Administration (VHA) Clinical Case Registry (CCR) which contains data on close to 60,000 current and former patients followed since 1984, provides an excellent source for addressing these important questions; and 2) a cross-sectional study comparing BMD and bone turnover markers (BTMs) between HIV/HCV co-infected, HIV and HCV mono-infected patients receiving care at the VA North Texas Health Care System (VANTHCS), with 650 current HIV patients (1/3 co-infected with HCV) and close to 5000 HCV patients. The current proposed work will address three specific aims: 1) To determine the impact of ART on bone health in HIV-infected patients. Using the CCR, osteoporotic fractures will be identified by ICD-9 code. Age-adjusted standardized incidence rates (SIRs) of osteoporotic fractures will be calculated and compared between the pre-HAART (1984-1995) and HAART (1996-2009) eras. Survival analyses will then be performed predicting onset of fractures among HIV-infected patients with various ARTexposure as time-dependent variables; 2) To determine the impact of HCV co-infection on bone health in HIV patients. We will assess BMD, BTMs, calciotropic and gonadal hormones and inflammatory cytokines in HIV/HCV co-infected patients and age-, gender-, and race-matched HIV mono-infected patients and HCV mono-infected patients receiving care at the VANTHCS. The ANOVA analysis will be conducted to detect difference among the three groups of patients. Age-adjusted SIRs of osteoporotic fractures will be computed and compared between HIV/HCV co- infected and HIV-only infected patients. We will further compare the SIRs within the pre-HAART and HAART eras; 3) To determine the association of decreased bone health and osteoporotic fractures with morbidity and mortality of HIV-infected patients. In the cross-sectional analysis, we will evaluate the correlation of dyslipidemia, insulin resistance and hyperlactatemia with BMD and BTMs. Furthermore, we will use the CCR data to explore whether dyslipidemia, hyperglycemia and hyperlactemia predict the onset of osteoporotic fractures by including them into the Cox survival model as time-dependent covariates. Finally, survival models will be constructed from CCR data to explore the association of osteoporotic fractures with all- cause mortality, AIDS and non-AIDS-related mortality.

描述（由申请人提供）： 自从采用高效抗逆转录病毒疗法（HAART）以来，随着艾滋病毒感染患者生存率的提高，低骨量和骨质疏松性骨折似乎正在成为影响老龄化艾滋病毒阳性人群的重要慢性问题。此外，估计15%至30%的HIV感染患者合并感染丙型肝炎（HCV），也与骨质疏松症有关。对于给定的骨矿物质密度（BMD）降低，骨折风险在一般人群中随着年龄的增长而显著增加。尽管如此，在一个大型的艾滋病毒队列骨折风险的趋势从来没有被评估，以确定这是否是一个日益严重的问题，艾滋病毒感染的患者，也没有进行深入的评估风险因素，包括类型和持续时间的抗逆转录病毒治疗（ART）和HCV合并感染。此外，与HCV感染相关的因素可能介导HIV感染患者骨密度降低和骨质疏松性骨折（形成减少或吸收增加）的风险增加，但尚未阐明。最后，骨质疏松性骨折对艾滋病相关和非艾滋病相关发病率和死亡率的影响尚不清楚。我们建议通过以下方式帮助弥合这些知识差距：1）回顾性分析退伍军人健康管理局（VHA）临床病例登记处（CCR）中的骨质疏松性骨折风险，其预测因素和结局，该登记处包含自1984年以来随访的近60，000名当前和以前患者的数据，为解决这些重要问题提供了极好的来源;和2）一项横断面研究，比较了在VA北德克萨斯卫生保健系统（VANTHCS）接受治疗的HIV/HCV共感染、HIV和HCV单一感染患者之间的BMD和骨转换标志物（BTM），其中有650名目前的HIV患者（1/3共感染HCV）和近5000名HCV患者。目前拟议的工作将解决三个具体目标： 1)确定ART对HIV感染患者骨骼健康的影响。使用CCR，将通过ICD-9代码识别骨化性骨折。将计算并比较HAART前（1984-1995）和HAART（1996-2009）时期的经神经外科调整的标准化骨折发生率（SIR）。然后将进行生存分析，预测以各种ART暴露作为时间依赖变量的HIV感染患者的骨折发作; 2)确定HCV合并感染对HIV患者骨健康的影响。我们将评估HIV/HCV合并感染患者以及年龄、性别和种族匹配的HIV单一感染患者和在VANTHCS接受治疗的HCV单一感染患者的BMD、BTM、促钙激素和性腺激素以及炎症细胞因子。将进行ANOVA分析，以检测三组患者之间的差异。将计算并比较HIV/HCV合并感染患者和仅HIV感染患者之间的腰椎间盘突出骨折的经调整的SIR。我们将进一步比较前HAART和HAART时代的SIR; 3)确定HIV感染患者骨健康状况下降和骨质疏松性骨折与发病率和死亡率的关系。在横断面分析中，我们将评估血脂异常、胰岛素抵抗和高乳酸血症与BMD和BTM的相关性。此外，我们将使用CCR数据，通过将血脂异常、高血糖症和高乳酸血症作为时间依赖性协变量纳入考克斯生存模型，探讨其是否可预测骨质疏松性骨折的发生。最后，将根据CCR数据构建生存模型，以探讨骨质疏松性骨折与全因死亡率、AIDS和非AIDS相关死亡率的关系。